Prostate Cancer: Driving the Personalized Medicine Highway

Howard Wolinsky decides it may all be in the genes

Howard Wolinsky a journalist based in the Chicago area, was diagnosed with early prostate cancer in 2010. In part one of this series he described his diagnosis and his decision to chose active surveillance. In the second part, he shared his experience during 5 years of active surveillance and in this part he tells his continuing quest to make the best -- and most informed -- decision about his care.

A quiet revolution is unfolding in the treatment of early-stage prostate cancer.

A growing number of men with Gleason 6 cancers are rejecting the urge to be whisked off to surgery and radiotherapy to seek cures. Likewise, men are learning that these slow-growing tumors are unlikely to kill them. Also, they want to avoid common side effects from treating a slow-growing tumor, such as erectile dysfunction and urinary incontinence.

In the Beginning ...

I was diagnosed with Gleason 6 prostate cancer at age 63 in 2010. At that time, fewer than 10% of men opted for active surveillance, which includes PSA tests every 3 to 6 months and biopsies annually or biannually. I took my chances with active surveillance.

Now, though estimates vary, as many as 40%-50% of men choose active surveillance, according to my urologist Scott Eggener, MD, who launched an active surveillance program at the University of Chicago Medical Center in 2008.

Also, he cited Michigan Urological Surgery Improvement Collaborative (MUSIC) study, finding that about half of men with low-risk cancer initially adopted active surveillance though rates varied considerably in different practices.

When I started on active surveillance in 2010, the available research was a Canadian 10-year survival study that provided enough information for me to be fairly confident that the odds favored my tiny cancer would look pretty much the same in 2020 as it did in 2010.

So far, so good, 5 years into active surveillance.

I've had four biopsies since 2010 when my PSA started to increase. The first was inconclusive. The second found a tiny adenocarcinoma, one millimeter in length, classified as a Gleason 6. My next two biopsies in 2011 and 2012 found no cancer at all though Eggener informed me I still had cancer, but he put me on a biopsy holiday.

The good news continued in 2015 with the publication of 15-year survival data from the Canadian researchers.

Writing in the Journal of Clinical Oncology, Laurence Klotz, MD, and colleagues from the University of Toronto reported in the Journal of Clinical Oncology in January 2015: "Active surveillance for favorable-risk prostate cancer is feasible and seems safe in the 15-year time frame. In our cohort, 2.8% of patients have developed metastatic disease, and 1.5% have died of prostate cancer."

As a patient with early prostate cancer, this was great news. I appreciated being able to follow a group of patients like me who have a 5-year head start.

Getting Personal

But while it feels good to have statistics on your side, they are still statistics. I had my eye out for anything offering personalized data to indicate whether I had made the right choice with active surveillance.

In April 2013, I read about a study in the Journal of Urology suggesting that genetic testing might provide some answers on PSA that would indicate a need for a biopsy.

Brian Helfand, MD, [remember that name] a urologist from NorthShore University HealthSystem in the Chicago suburbs, and his colleagues found that four single nucleotide polymorphisms could be used to adjust a man's measured PSA concentration and potentially delay or prevent unnecessary prostate biopsies in Caucasian men.

"By utilizing a person's genetic makeup we can personalize care when he comes in for a PSA screening," said Helfand. "We may be able to prevent some men from having an unnecessary biopsy and prevent a delay in biopsy for men who may have an aggressive disease."

For 98% of the men, genetic adjustment of PSA levels did not change the outcome of their screening. But the genetic correction was important for the 17 men reclassified as no longer meeting biopsy criteria and the three whose condition was up-classified, and it was recommended they get a biopsy, based on their genetic adjustment.

I was excited to read that -- finally here was something that might enable met to avoid some biopsies.

As it happens, I was an early adopter of DNA testing for family history and health reasons over the past 15 years or so. I was among the customers at FamilyTreeDNA and 23andMe. I used the SNP browser at 23andMe and pulled up the four markers mentioned in the study.

I shared the report and my markers with Eggener, who informed me he was familiar with it, but stressed that the test was not commercially available.

In June 2014, a friend sent me a report about another genetic test, which claimed to be the first and only proteomic-based imaging biopsy test to differentiate accurately between aggressive and non-aggressive forms of prostate cancer at early stages of the disease.

Eggener was skeptical about the relevance of such tests for me: "That test, along with a few others (4K, phi) are new; data suggests mildly helpful for screening patients without prostate cancer, not for guys like you with known diagnosis."

Asking the Question

Then on Dec. 2, 2015, as a journalist who often wrote about DNA testing, I made some appointments at the NorthShore University HealthSystem Center for Personalized Medicine to learn about new genomic approaches being commercialized and studied there.

I interviewed two physician-researchers, Charles Brendler, MD, and Jianfeng Xu, MD, DrPH, about translational genomic research performed at their hospital system, which has an academic affiliation the University of Chicago Pritzker School of Medicine.

Xu, formerly of the Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, has been working on a genetic risk score to determine the likelihood of a patient developing prostate cancer (among other cancers). Data have shown that this genetic risk score may also be associated with the aggressiveness of prostate cancer.

Genetic data from more than 100,000 patients with or without prostate cancer were used to create a genetic risk score to predict prostate cancer. Xu said prospective studies still need to be conducted for the score to be commercialized. Patients with mutations in several cancer genes are more likely to die of prostate cancer. Xu said 10-20% of prostate cancer patients with aggressive disease had mutations in these genes.

But his approach is considered experimental, the personalized risk assessment is not ready for prime time.

I met with Brendler and Xu as a journalist, but I wondered if they would recommend further testing for me, so I asked.

They did, including the genetic risk score.

Brendler said, "You know your PSA and your Gleason score and your volume of tumor, but you don't have genetic characterization of the tumor, which would tell you how aggressive the cancer is."

He also suggested that I see urologist Brian Helfand, who runs NorthShore's personalized risk-assessment prostate cancer clinic, which has 370 patients following its protocol. (Yes, the same Helfand who led the study I mentioned earlier.)

It felt a little bit like cheating on Eggener, my urologist of the past 5 years. I explained my hesitation and Xu helpfully noted: "This will give you a second opinion. You should think that way about it."

I informed Eggener about my plan. He endorsed Helfand. The two urologists knew each other from their residencies at Northwestern Memorial Hospital in Chicago.

Pedal to the Metal

On Dec. 30, my wife Judi and I saw Helfand.

Helfand, who has a breezy style and fessed up to being a fan of the same Chicago hot dog joint I like, recommended that I have Beckman Coulter's Prostate Health Index assay, which was approved by the FDA in2012, the FDA as an aid to distinguish prostate cancer from benign prostatic conditions in men 50 years of age and older with total PSA results in the 4 – 10 ng/mL range and negative digital rectal examination findings. The assay is supposed to bethree times more accurate for prostate cancer detection than PSA testing by itself.

Helfand explained that "phi is not approved for prostate cancer screening. It is FDA approved only to predict biopsy outcomes. Therefore, phi has implied utility for men undergoing AS, because it is associated with high-grade disease."

He said phi and 4kscore from OPKO Lab are two options to predict the presence of aggressive disease. "High grade/more aggressive disease is one of the most important factors that we use in determining which patients will do well while on active surveillance," he told me.

On Jan. 8, 2016, I again drove 50 miles from my house in the far south suburbs of Chicago to NorthShore University's ambulatory care center in the far northern suburbs to undergo a phi. I was promised results in 3 weeks.

Helfand and Eggener both recommended a focused MRI, which I have scheduled.

The phi and the focused MRI represent refinements to this new path of active surveillance. These combined results will, I hope, guide my future path.

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